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Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis 被引量:1
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作者 Jiaqi Tang Lin Luo +18 位作者 Bakwatanisa Bosco Ning Li Bin Huang Rongrong Wu Zihan Lin Ming Hong Wenjie Liu Lingxiang Wu Wei Wu Mengyan Zhu Quanzhong Liu Peng Xia Miao Yu Diru Yao Sali Lv Ruohan Zhang Wentao Liu Qianghu Wang Kening Li 《Journal of Biomedical Research》 CAS CSCD 2024年第4期397-412,共16页
Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been s... Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy. 展开更多
关键词 acute myeloid leukemia cell surface markers PROGNOSIS drug sensitivity multi-model analysis
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Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients 被引量:3
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作者 Jian-Hua Yu Jing-Tao Dong +5 位作者 Yong-Qian Jia Neng-Gang Jiang Ting-Ting Zeng Hong Xu Xian-Ming Mo Wen-Tong Meng 《Chinese Journal of Cancer》 SCIE CAS CSCD 2013年第4期213-223,共11页
Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL... Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL. 展开更多
关键词 COMMON b-cell acute LYMPHOBLASTIC leukemia immunophenotype diagnosis heterogeneity flow CYTOMETRY
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Non-canonical BRAF variants and rearrangements in hairy cell leukemia
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作者 STEPHEN E.LANGABEER 《Oncology Research》 SCIE 2024年第9期1423-1427,共5页
Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical profile.The vast majority of HCL patients harbor the canonical BRAF V600E mutation whi... Hairy cell leukemia(HCL)is an uncommon mature B-cell malignancy characterized by a typical morphology,immunophenotype,and clinical profile.The vast majority of HCL patients harbor the canonical BRAF V600E mutation which has become a rationalized target of the subsequently deregulated RAS-RAF-MEK-MAPK signaling pathway in HCL patients who have relapsed or who are refractory to front-line therapy.However,several HCL patients with a classical phenotype display non-canonical BRAF mutations or rearrangements.These include sequence variants within alternative exons and an oncogenic fusion with the IGH gene.Care must be taken in the molecular diagnostic work-up of patients with typical HCL but without the BRAF V600E to include investigation of these uncommon mechanisms.Identification,functional characterization,and reporting of further such patients is likely to provide insights into the pathogenesis of HCL and enable rational selection of targeted inhibitors in such patients if required. 展开更多
关键词 Hairy cell leukemia BRAF Molecular diagnostics Targeted therapy
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Treatment refractory mast cell leukemia with dominant gastrointestinal manifestation and concomitant skin symptoms:A case report
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作者 Maciej Tomasz Wysocki Maciej Gonciarz Bartosz Puła 《World Journal of Clinical Cases》 SCIE 2024年第20期4317-4324,共8页
BACKGROUND Mast cell leukemia(MCL),a subtype of systemic mastocytosis(SM),is an extremely rare clinical entity characterized by a very poor prognosis.Chemotherapy,tyrosine kinase inhibitors,and allogeneic hematopoieti... BACKGROUND Mast cell leukemia(MCL),a subtype of systemic mastocytosis(SM),is an extremely rare clinical entity characterized by a very poor prognosis.Chemotherapy,tyrosine kinase inhibitors,and allogeneic hematopoietic cell transplantation are the only treatment options,but they cannot provide the desired outcomes in most cases of MCL.However,other types of SM can be successfully treated.The disease has no specific manifestation,but gastroenterological symptoms are present in most cases.CASE SUMMARY The authors,hereby,report a case of a 46-year-old female patient diagnosed with MCL-the rarest subtype of SM.The patient presented to the gastroenterology clinic with multiple,various,and unspecific gastroenterological symptoms.Concomitance of skin lesions significantly contributed to a relatively prompt diagnosis.The serum tryptase level was extremely high and bone the marrow aspirate showed an infiltration of atypical mast cells.The disease was rapidly progressive and primary refractory to chemotherapy and the patient succumbed to the illness about a month after the initiation of treatment.CONCLUSION Despite its“hematological nature”,MCL,in most cases presents dominantly with unspecific gastroenterological symptoms.Thus,a high disease awareness among physicians other than hematologists is necessary to improve treatment outcomes.Serum tryptase level,due to its non-invasive nature and easy access,may serve as an initial step to estimate the probability of mastocytosis. 展开更多
关键词 MASTOCYTOSIS Systemic mastocytosis Mast cell leukemia TRYPTASE Case report
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Quality-adjusted time without symptoms or toxicity analysis of haploidentical-related donor vs.identical sibling donor hematopoietic stem cell transplantation in acute myeloid leukemia
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作者 Yuewen Wang Xianli Gao +12 位作者 Ting Wang Xiaohui Zhang Lanping Xu Yu Wang Chenhua Yan Huan Chen Yuhong Chen Wei Han Fengrong Wang Jingzhi Wang Xia Yan Xiaodong Mo Xiaojun Huang 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2024年第5期530-544,共15页
Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematop... Objective:We aimed to compare the quality-adjusted time without symptoms or toxicity(Q-TWiST)in acute myeloid leukemia(AML)patients who received haploidentical-related donor(HID)and identical sibling donor(ISD)hematopoietic stem cell transplantation(HSCT).Methods:Five clinical health states were defined:toxicity(TOX),acute graft-versus-host disease(GVHD),chronic GVHD(cGVHD),time without symptoms and toxicity(TWiST)and relapse(REL).The equation used in this study was as follows:Q-TWiST=UTOX×TOX+UTWiST×TWiST+UREL×REL+UaGVHD×aGVHD+UcGVHD×cGVHD.Results:A total of 239 AML patients were enrolled.We established a mathematical model,i.e.,Q-TWiST HID HSCT>Q-TWiST ISD HSCT,to explore the range of utility coefficients satisfying the inequality.Based on the raw data,the utility coefficient is equivalent to the following inequality:10.57067UTOX-46.27733UREL+105.9374+3.388078UaGVHD-210.8198UcGVHD>0.The model showed that when UTOX,UREL,and UaGVHD were within the range of 0-1,as well as when UcGVHD was within the range of 0-0.569,the inequality Q-TWiST HID HSCT>Q-TWiST ISD HSCT was valid.According to the results of the ChiCTR1800016972 study,the median coefficients of TOX,acute GVHD(aGVHD),and cGVHD were 0.56(0.41-0.76),0.56(0.47-0.72),and 0.54(0.37-0.79),respectively.We selected a series of specific examples of the coefficients,i.e.,UTOX=0.5,UREL=0.05,UaGVHD-0.5,and UcGVHD-0.5.The Q-TWiST values of ISD and HID HSCT were 896 and 900 d,respectively(P=0.470).Conclusions:We first observed that Q-TWiST was comparable between AML patients receiving HID HSCT and those receiving ISD HSCT. 展开更多
关键词 Quality-adjusted time without symptoms or toxicity acute myeloid leukemia allogeneic hematopoietic stem cell transplantation HAPLOIDENTICAL
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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction
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作者 Cheng-Jin Ai Ling-Juan Chen +2 位作者 Li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao 《World Journal of Stem Cells》 SCIE 2024年第4期444-458,共15页
BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against... BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML. 展开更多
关键词 leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling
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Prognostic Significance of Apoptosis Regulators in B-Cell Chronic Lymphocytic Leukemia
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作者 Ahmad Baraka Shereen El Shorbagy +4 位作者 Ola M. Elfarargy Rasha Haggag Lobna A. Abdelaziz Salah F. Elsayed Khaled A. Elbana 《Journal of Cancer Therapy》 2017年第4期360-385,共26页
Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL.... Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL. 展开更多
关键词 MYELOID cell leukemia 1 b-cell LYMPHOMA 2 BAX b-cell Chronic LYMPHOCYTIC leukemia
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Mutation Analysis of IgVH Gene in B-Cell Chronic Lymphocytic Leukemia
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作者 王峰 朱慧芬 +2 位作者 朱丽娟 殷波涛 沈关心 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2002年第3期177-179,182,共4页
Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2... Summary: The variable heavy chain region (VH) genes of 3 untreated patients with B cell chronic lymphocytic leukemia (B CLL) were cloned and analyzed. The VH family used was VH3 11, VH3 72 and VH3 33. More than 2 % difference from the corresponding germline gene was detected in all the 3 obtained potential functional genes (average 16.7). Mutation pattern analysis indicated evidence of antigen selective pressure observed in 1 of 3 cases. Our findings suggested that the tumor cells originate from post GC cells. 展开更多
关键词 immunoglobulin variable region mutation analysis B cell chronic lymphocytic leukemia
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Expression pattern of BIM,BCL-6,and c-MYC in adult B-cell acute lymphoblastic leukemia
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作者 Chanli Zheng Lin Xu +2 位作者 Yanjun Xie Dongmei He Yangqiu Li 《Oncology and Translational Medicine》 2017年第4期151-155,共5页
Objective We aimed to evaluate the expression pattern of the genes BIM, BCL-6, and c-MYC in adult patients at initial diagnosis of B-cell acute lymphoblastic leukemia(B-ALL).Methods Relative m RNA levels of BIM, BCL-6... Objective We aimed to evaluate the expression pattern of the genes BIM, BCL-6, and c-MYC in adult patients at initial diagnosis of B-cell acute lymphoblastic leukemia(B-ALL).Methods Relative m RNA levels of BIM, BCL-6, and c-MYC in peripheral blood mononuclear cells(PBMCs) from B-ALL patients were determined by quantitative reverse-transcription polymerase chain reaction(q RT-PCR) using SYBR Green dye. PBMCs from healthy volunteers served as a control. GAPDH was used as a reference gene.Results Relative expression of BIM, BCL-6, and c-MYC m RNA in B-ALL patients was significantly lower than in healthy controls(P < 0.05). Furthermore, this result was observed for both newly diagnosed B-ALL patients and those incomplete remission(CR)(P < 0.05). There were no statistically significant differences in the expression levels of BIM, BCL-6, and c-MYC between these B-ALL patient groups(P > 0.05). Spearman's rank correlation analyses revealed the expression level of BIM to be positively correlated with that of BCL-6 in B-ALL patients.Conclusion Expression of the genes BIM, BCL-6, and c-MYC is decreased in adult B-ALL patients. Moreover, the expression pattern of these genes may be similar in such patients at initial diagnosis and following CR. The expression characteristics of BIM, BCL-6, and c-MYC may constitute useful markers for the diagnosis of adult B-ALL. 展开更多
关键词 BIM BCL-6 C-MYC B cell acute LYMPHOBLASTIC leukemia (ALL) quantitative REVERSETRANSCRIPTION polymerase chain reaction (qRT-PCR)
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Diphtheria Toxin/Human B-Cell Activating Factor Fusion Protein Kills Human Acute Lymphoblastic Leukemia BALL-1 Cells: An Experimental Study
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作者 Xin-pu Gao Zheng-min Liu +5 位作者 Yu-lian Jiao Bin Cui Yue-ting Zhu Jie Zhang Lai-cheng Wang Yue-ran Zhao 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2012年第3期238-244,共7页
Objective: This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor (DT388sBAFF) in Escherichia coli (E. coli) and investigate its activity in human B-lineage acute lymp... Objective: This study aimed to express a fusion protein of diphtheria toxin and human B cell-activating factor (DT388sBAFF) in Escherichia coli (E. coli) and investigate its activity in human B-lineage acute lymphoblastic leukemia 1 cells (BALL-1). Methods: A fragment of DT388sBAFF fusion gene was separated from plasmid pUC57-DT388sBAFF digested with Nde I and Xho I, and inserted into the expression vector pcold II digested with the same enzymes. Recombinants were screened by the colony polymerase chain reaction (PCR) and restriction map. The recombinant expression vector was transformed into BL21 and its expression was induced by isopropyl β-D-1-thiogalactopyranoside (IPTG). The recombinant protein was identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot, and then purified by Ni2+-NTA affinity chromatography. The expression level of B cell-activating factor receptor (BAFF-R) on BALL-1 cells was assessed by real-time PCR. The receptor binding capacity of recombinant protein was determined by cell fluorescent assay. The specific cytotoxicity of recombinant protein on BALL-1 cells was detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The expression level of recombinant protein was 50% of total bacterial proteins in E. coli, and the recombinant protein could bind to BAFF-R-positive BALL-1 cells and thereby produce a cytotoxic effect on the cells. Conclusion: The fusion protein expression vector DT388sBAFF was successfully constructed and the recombinant protein with selective cytotoxicity against BALL-1 cells was obtained, providing foundation for further study of the therapy of human B-lineage acute lymphoblastic leukemia. 展开更多
关键词 B cell-activating factor b-lineage acute lymphoblastic leukemia Diphtheria toxin Fusion protein
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B-cell lymphoma-2 inhibition and resistance in acute myeloid leukemia
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作者 Lindsay Wilde Sabarina Ramanathan Margaret Kasner 《World Journal of Clinical Oncology》 CAS 2020年第8期528-540,共13页
Spurred by better understanding of disease biology,improvements in molecular diagnostics,and the development of targeted therapies,the treatment of acute myeloid leukemia(AML)has undergone significant evolution in rec... Spurred by better understanding of disease biology,improvements in molecular diagnostics,and the development of targeted therapies,the treatment of acute myeloid leukemia(AML)has undergone significant evolution in recent years.Arguably,the most exciting shift has come from the success of treatment with the B-cell lymphoma-2 inhibitor venetoclax.When given in combination with a hypomethylating agent or low dose cytarabine,venetoclax demonstrates high response rates,some of which are durable.In spite of this,relapses after venetoclax treatment are common,and much interest exists in elucidating the mechanisms of resistance to the drug.Alterations in leukemic stem cell metabolism have been identified as a possible escape route,and clinical trials focusing on targeting metabolism in AML are ongoing.This review article highlights current research regarding venetoclax treatment and resistance in AML with a focus on cellular metabolism. 展开更多
关键词 Acute myeloid leukemia b-cell lymphoma-2 Venetoclax METABOLISM Leukemic stem cell RESISTANCE
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Bortezomib-Induced Bilateral Eye Swelling and Cutaneous Adverse Reaction in a Patient with Plasma Cell Leukemia—A Case Report
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作者 Azeezat Ariwoola Ehab A. M. Elagab +6 位作者 Tahira Fardous Saburi Oyewale Sara Parisi Heather Williams Amal M. Shediwah Islam A. Mahmoud Ratesh Khillan 《Case Reports in Clinical Medicine》 2023年第11期452-456,共5页
Bortezomib, a proteasome inhibitor, is an established therapy against plasma cell leukemia—a variant of plasma cell dyscrasias. Its most frequent side effects have been listed as peripheral neuropathy, neuropathic pa... Bortezomib, a proteasome inhibitor, is an established therapy against plasma cell leukemia—a variant of plasma cell dyscrasias. Its most frequent side effects have been listed as peripheral neuropathy, neuropathic pain, thrombocytopenia, and gastrointestinal problems. Allergic skin reaction is a rarely documented side effect in patients receiving bortezomib-based chemotherapy. A combination therapy consisting of intravenous bortezomib, oral Revlimid tablets, and oral dexamethasone tablets has been prescribed for the patient after his recent diagnosis of plasma cell leukemia. While receiving his third treatment cycle, he developed an allergic reaction (skin rash) involving the neck, and wrists, and mild bilateral eye swelling. The infusion was stopped immediately and then ciprofloxacin ophthalmic solution and oral diphenhydramine 25 mg were prescribed to the patient with significant improvement in his clinical condition. He was temporarily taken off bortezomib. At a follow-up visit a week later, a significant improvement was noticed in his condition. Rash had reduced on neck and wrists, and eye swelling had reduced as well. As of the time of writing this case report, he has been temporarily taken off bortezomib, but other medications in the treatment regimen were continued as prescribed. 展开更多
关键词 Plasma cell leukemia HEMATOLOGY BORTEZOMIB CHEMOTHERAPY
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THE ULTRASTRUCTURAL STUDY OF NON-HODGKIN'S LYMPHOMA CELL,CHRONIC LYMPHOCYTIC AND HAIRY CELL LEUKEMIA
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作者 归薇 张巧花 +2 位作者 郑玉萍 贺建霞 王列样 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1996年第2期140-143,共4页
Non-Hodgkin’s lymphoma cell leukemia (NHLCL),chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HLC) are the diseases very similar to each other. The differential diagnosis is very difficult,especially when ... Non-Hodgkin’s lymphoma cell leukemia (NHLCL),chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HLC) are the diseases very similar to each other. The differential diagnosis is very difficult,especially when there are small lymphoid cells in Periphcral blood and bone marrow under light microscope. We have observed 34 cases with electron microscope. The studies were correlated with clinical manifestation, cytology, pathology and immunologic histochemistry. Ultrastructural features strongly indicated the difference in three various diseases, although all the immunologic markers showed B-cell type.It is concluded that electron microscopic examination is of a definite significance in the diaguosis and successful treatment. 展开更多
关键词 ULTRASTRUCTURE Non- Hodgkin's lymphoma cell leukemia Chronic lymphocytic leukemia hairy cell leukemia
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Resveratrol-downregulated Phosphorylated Liver Kinase B1 Is Involved in Senescence of Acute Myeloid Leukemia Stem Cells 被引量:7
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作者 彭丹月 宋慧 刘凌波 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2015年第4期485-489,共5页
Summary: Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of res... Summary: Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB 1 and Sirtuin 1 (SIRT1), a regulator ofpLKB1, were measured in CD34+CD38-KGla cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell pro- liferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34+CD38- KGla cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34+CD38- KGla cells. It was concluded that resveratrol-downregulated pLKB1 is in- volved in the senescence of AML stem cells. 展开更多
关键词 phosphorylated liver kinase B1 (pLKB1) Sirtuin 1 (SIRT1) RESVERATROL acute myeloid leukemia (AML) leukemia stem cells (LSCs) cellular senescence
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Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang 被引量:8
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作者 Hong-Sheng Zhou Bing Z.Carter Michael Andreeff 《Cancer Biology & Medicine》 SCIE CAS CSCD 2016年第2期248-259,共12页
Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity t... Acute myeloid leukemia (AML) is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow (BM) niche is critical to the maintenance and retention of hematopoietic stem cells (HSC), including leukemia stem cells (LSC), and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors. 展开更多
关键词 Bone marrow niche leukemia stem cell acute myeloid leukemia Yin and Yang
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Allogeneic hematopoietic stem cell transplantation for patients with acute leukemia 被引量:3
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作者 Yan Chen Yajing Xu +12 位作者 Gan Fu Yi Liu Jie Peng Bin Fu Xiaoyu Yuan Hongya Xin Yan Zhu Qun He Dengshu Wu Yigang Shu Xiaolin Li Xielan Zhao Fangping Chen 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2013年第4期389-396,共8页
Objective: The purposes of this study were to assess the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia (AL) and analyze the factors affecting the prognosis of these pati... Objective: The purposes of this study were to assess the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia (AL) and analyze the factors affecting the prognosis of these patients. Methods: The clinical and follow-up data of 93 AL patients (median age, 30 years) undergoing allogeneic HSCT in Xiangya Hospital over the past 12 years were collected, and the potential factors affecting the efficacy and prognosis of allogeneic HSCT patients were determined. Results: Hematopoietic reconstitution was achieved in 90 patients. At the last follow-up, the incidences of severe acute graft versus host disease (aGvHD) and extensive chronic GvHD (cGvHD) were 14.0% and 20.0%, the 3-year cumulative incidence of transplantation related mortality (TRM) and relapse rate were 16.8%±6.1% and 21.3%±6.7%, and the estimated 3-year overall survival (OS) and disease-free survival (DFS) of the patients were 64.6%±5.4% and 56.5%±5.5%, respectively. Univariate analysis indicated that age older than 40 years, HLA mismatch, and severe lung infection within the first 100 days after transplantation were risk factors for severe aGvHD, age older than 40 years, HLA mismatch, severe lung infection within the first 100 days after transplantation, and severe aGvHD were risk factors for TRM, high-risk AL and lack of cGvHD were risk factors for relapse (all P〈0.05). Survival estimation showed that HLA mismatch, severe lung infection occurring within the first 100 days post-transplantation, high-risk AL severe aGvHD and lack of cGvHD were risk factors associated with poor prognosis (all P〈0.05). Further multivariate analyses revealed that severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD were independent risk factors for unfavorable outcomes (all P〈0.05). Conclusions: Allogeneic HSCT can improve the DFS of AL patients, and severe lung infection within the first 100 days post-transplantation, severe aGvHD and lack of cGvHD are independent risk factors affecting the prognosis. 展开更多
关键词 leukemia hematopoietic stem cell transplantation (HSCT) graft-versus-leukemia effect
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Murine models based on acute myeloid leukemia-initiating stem cells xenografting 被引量:2
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作者 Cristina Mambet Mihaela Chivu-Economescu +4 位作者 Lilia Matei Laura Georgiana Necula Denisa Laura Dragu Coralia Bleotu Carmen Cristina Diaconu 《World Journal of Stem Cells》 SCIE CAS 2018年第6期57-65,共9页
Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based ... Acute myeloid leukemia(AML) is an aggressive malignant disease defined by abnormal expansion of myeloid blasts. Despite recent advances in understanding AML pathogenesis and identifying their molecular subtypes based on somatic mutations, AML is still characterized by poor outcomes, with a 5-year survival rate of only 30%-40%, the majority of the patients dying due to AML relapse. Leukemia stem cells(LSC) are considered to be at the root of chemotherapeutic resistance and AML relapse. Although numerous studies have tried to better characterize LSCs in terms of surface and molecular markers, a specific marker of LSC has not been found, and still the most universally accepted phenotypic signature remains the surface antigens CD34+CD38- that is shared with normal hematopoietic stem cells. Animal models provides the means to investigate the factors responsible for leukemic transformation, the intrinsic differences between secondary post-myeloproliferative neoplasm AML and de novo AML, especially the signaling pathways involved in inflammation and hematopoiesis. However, AML proved to be one of the hematological malignancies that is difficult to engraft even in the most immunodeficient mice strains, and numerous ongoing attempts are focused to develop "humanized mice" that can support the engraftment of LSC. This present review is aiming to in-troduce the field of AML pathogenesis and the concept of LSC, to present the current knowledge on leukemic blasts surface markers and recent attempts to develop best AML animal models. 展开更多
关键词 Acute MYELOID leukemia leukemia-initiating stem cells ANTIGEN markers MURINE models XENOGRAFTS
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Update on acute myeloid leukemia stem cells:New discoveries and therapeutic opportunities 被引量:3
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作者 Maximilian Stahl Tae Kon Kim Amer M Zeidan 《World Journal of Stem Cells》 SCIE CAS 2016年第10期316-331,共16页
The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use ... The existence of cancer stem cells has been wellestablished in acute myeloid leukemia. Initial proof of the existence of leukemia stem cells(LSCs) was accomplished by functional studies in xenograft models making use of the key features shared with normal hematopoietic stem cells(HSCs) such as the capacity of self-renewal and the ability to initiate and sustain growth of progenitors in vivo. Significant progress has also been made in identifying the phenotype and signaling pathways specific for LSCs. Therapeutically, a multitude of drugs targeting LSCs are in different phases of preclinical and clinical development. This review focuses on recent discoveries which have advanced our understanding of LSC biology and provided rational targets for development of novel therapeutic agents. One of the major challenges is how to target the selfrenewal pathways of LSCs without affecting normal HSCs significantly therefore providing an acceptable therapeutic window. Important issues pertinent to the successful design and conduct of clinical trials evaluating drugs targeting LSCs will be discussed as well. 展开更多
关键词 leukemia stem cells Cancer stem cells Acute myeloid leukemia Stem cell niche XENOTRANSPLANTATION PLERIXAFOR NF-κ B C-X-C chemokine receptor type 4
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PATHOLOGICAL STUDIES ON THE ANTI-INVASIVE CHARACTER BY RECOMBINANT HUMAN INTERLEUKIN-6 GENE-TRANSFECTED MOUSE LEUKEMIA CELLS
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作者 葛林阜 曹雪涛 +4 位作者 马大烈 李劲松 张福州 于益芝 叶天星 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 1996年第4期249-252,共4页
Mouse FBL-3 erythroleukemia cells were transfected with recombinant human interleukin-6 (rhIL-6) gene and a clone secreting IL-6 was selected (i.e., FBL-3-IL-6+). The cell clone secreting IL-6 was inoculated into C57B... Mouse FBL-3 erythroleukemia cells were transfected with recombinant human interleukin-6 (rhIL-6) gene and a clone secreting IL-6 was selected (i.e., FBL-3-IL-6+). The cell clone secreting IL-6 was inoculated into C57BL/6 mouse. The growth of tumors was observed and histologic analyses of the tumors in situ, liver, spleen and bone marrow were performed after inoculation. The mice inoculated with wild-type FBL-3 erythroleukemia cells were used as the control. The results showed that the later the tumor occurrence, the slower the tumor development,the lower the pathological changes degree and the longer the survival time in experimental group compared to that of the control. The results demonstrated that the inoculation of the FBL-3 cell clone secreting IL-6 can inhibit the invasion of leukemia cells, suggesting that the FBL-3-IL-6+ cells can he used as a vaccine to treat leukemia. 展开更多
关键词 leukemia Experimental interleujin-6 gene transfer Invasion of leukemia cells
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Study of Heat Shock Protein HSP90α,HSP70,HSP27 mRNA Expression in Human Acute Leukemia Cells
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作者 肖侃艳 刘文励 +2 位作者 屈伸 孙汉英 唐锦治 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 1996年第4期212-216,共5页
The expression of three heat shock proteins (HSPs)-HSP90, HSP70,HSP27 in cells obtained from 22 patients with leukemia, K562 erythroleukemia cell line, and normal blood cells was observed by means of RNA dot blot anal... The expression of three heat shock proteins (HSPs)-HSP90, HSP70,HSP27 in cells obtained from 22 patients with leukemia, K562 erythroleukemia cell line, and normal blood cells was observed by means of RNA dot blot analysis.The results showed that the expression of the HSP27 gene was enhanced in 4 cases of acute lymphoid leukemia (ALL), 7 cases of acute nonlymphoid leukemia (ANLL) and 2 cases of myelodysplastic syndrome (MDS) as compared with that of the normal blood cells, yet there was no significant difference in the HSP27 expression between the ALL and ANLL cells. The expression of HSP70 in all the 5 ALL and ANLL patients was much lower than that of the normal subjects, except 1 case of ALL and 1 case of MDS, in which the expression was obviously enhanced. All the cases including 11 ANLL, 5 ALL and 1 MDS had higher HSP90α expression than the normal subjects. The enhanced expression of HSP90α in leukemia cells may be associated with the active and indefinite proliferation of leukemia cells. Our results also suggest that the high expression of the HSP27gene may not be confined to a specific type of acute leukemia. 展开更多
关键词 acute leukemia leukemia cell heat shock protein
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